The overall objective of this research is to analyze the relative contributions of genetically- and chemically-induced protein mistranslation and membrane deterioration as causes of cellular aging and death, employing primarily the fungus Neurospora crassa as a model. Our hypothesis predicts that these molecular errors are interrelated and that dietary antioxidants and membrane stabilizers should at least partially alleviate the aging process by preventing such errors. Nuclear mutants will be used to induce premature senescence in growth rate or viability. Drugs that induce protein mistranslation or membrane deterioration will be administered to wild type to induce premature senescence in growth rate. Reversal of genetically- or chemically-induced senescence by dietary antioxidants and membrane stabilizers will be sought. Biochemical and cytological co-relations with senescence will be sought by measurements of lipid autoxidation and fidelity of protein synthesis and observations of cell membranes in situ as a function of culture age and dietary supplements. The activities of antioxygenic enzymes, i.e. those that protect cells from oxygen toxicity and lipid autoxidation, will be measured in vitro in extracts of normal and senescent cells. The activities of microsomal and mitochondrial enzyme systems that catalyze lipid autoxidation will be measured. BIBLIOGRAPHIC REFERENCES: Colvin, H.J., M. Minssen, L. Kort, and K.D. Munkres. 1974. Neurospora crassa as a Model System for Studying the Process of Aging in Eukaryotic Organisms. Abstracts of the Annual Meeting - American Society of Microbiology. p. 179. Benveniste, K.B., and K.D. Munkres. 1975. Multiple Molecular Forms of Neurospora Mitochondrial Malate Dehydrogenase. in Isozymes I. Molecular Structure. C. Markert, editor. Academic Press, Inc. New York, p. 561-574.